Valine/isoleucine variants drive selective pressure in the VP1 sequence of EV-A71 enteroviruses.

BACKGROUND: In 2011-2012, Northern Vietnam experienced its first large scale hand foot and mouth disease (HFMD) epidemic. In 2011, a major HFMD epidemic was also reported in South Vietnam with fatal cases. This 2011-2012 outbreak was the first one to occur in North Vietnam providing grounds to study the etiology, origin and dynamic of the disease. We report here the analysis of the VP1 gene of strains isolated throughout North Vietnam during the 2011-2012 outbreak and before. METHODS: The VP1 gene of 106 EV-A71 isolates from North Vietnam and 2 from Central Vietnam were sequenced. Sequence alignments were analyzed at the nucleic acid and protein level. Gene polymorphism was also analyzed. A Factorial Correspondence Analysis was performed to correlate amino acid mutations with clinical parameters. RESULTS: The sequences were distributed into four phylogenetic clusters. Three clusters corresponded to the subgenogroup C4 and the last one corresponded to the subgenogroup C5. Each cluster displayed different polymorphism characteristics. Proteins were highly conserved but three sites bearing only Isoleucine (I) or Valine (V) were characterized. The isoleucine/valine variability matched the clusters. Spatiotemporal analysis of the I/V variants showed that all variants which emerged in 2011 and then in 2012 were not the same but were all present in the region prior to the 2011-2012 outbreak. Some correlation was found between certain I/V variants and ethnicity and severity. CONCLUSIONS: The 2011-2012 outbreak was not caused by an exogenous strain coming from South Vietnam or elsewhere but by strains already present and circulating at low level in North Vietnam. However, what triggered the outbreak remains unclear. A selective pressure is applied on I/V variants which matches the genetic clusters. I/V variants were shown on other viruses to correlate with pathogenicity. This should be investigated in EV-A71. I/V variants are an easy and efficient way to survey and identify circulating EV-A71 strains.

Re-positive testing, clinical evolution and clearance of infection: results from COVID-19 cases in isolation in Viet Nam

Objectives@#Asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and test re-positivity after a negative test have raised concerns about the ability to effectively control the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the prevalence of COVID-19 asymptomatic and pre-symptomatic infections during the second wave of COVID-19 in Viet Nam, and to better understand the duration of SARS-CoV-2 infection and the dynamics between the evolution of clinical symptoms and SARS-CoV-2 test positivity among confirmed COVID-19 cases.@*Methods@#We conducted a cohort analysis on the first 50 confirmed cases during the second COVID-19 wave in Viet Nam using clinical, laboratory and epidemiological data collected from 9 March to 30 April 2020. Kaplan-Meier estimates were used to assess time to clearance of SARS-CoV-2 infection, and log-rank tests were used to explore factors related to time to SARS-CoV-2 infection clearance.@*Results@#Most cases (58%) had no typical signs or symptoms of COVID-19 at the time of diagnosis. Ten cases (20%) were re-positive for SARS-CoV-2 during infection. Eight cases (16%) experienced COVID-19 symptoms after testing negative for SARS-CoV-2. The median duration from symptom onset until clearance of infection was 14 days (range: 6–31); it was longer in re-positive and older patients and those with pre-existing conditions.@*Conclusion@#Asymptomatic and pre-symptomatic infections were common during the second wave of COVID-19 in Viet Nam. Re-positivity was frequent during hospitalization and led to a long duration of SARS-CoV-2 infection.